Chapter 3 - Vessel wall biology Flashcards
Vessel wall characteristics: artery, vein, lymphatic
Collagen content
Elastic fiber content
Central pressure
Shear stress
Stretch force
Pulsatility
Compliance
Oxygen tension
Intrinsic propulsion
Valves
3 layers of the arterial wall
Tunica intima
Tunica media
Tunica adventitia
Thickness of vascular endothelium in capillaries/veins vs aorta
0.1 microm in capillaries/veins
1 microm in aorta
Coating on the vascular endothelium to reduce friction
Glycocalix
Thickness varies across vascular tree
Sheared off in inflammation to allow leukocyte attachment
Distance of intercellular space in the vascular endothelium
15-20 nm
Define: pinocytic vesicles
allow movement of material from vessel lumen into the wall
primarily in muscular small blood vessels, largely in heart and lung, less in retina and brain
Size of fenestrae on vascular endothelium
70 nm
majority have 5-6 nm nonmembranous diaphragm
Located in capillaries of exocrine/endocrine glands, GI mucosa, choroid plexus, glomeruli, renal tubules
Location of nonfenestrated continuous endothelium
Brain, skin, heart, lung
Location of discontinuous endothelium
size of their fenestrations
Liver
100-200 nm without diaphragm
Zones of the basal lamina
Lamina rara (inner): laminin (glycoprotein)
Lamina densa: fibrillar, dense next to interstitial connective tissue; type IV collagen
Endothelium in normal functioning
Quiescent state
Cell-cell contact inhibit proliferation
Low mitotic index
Secrete ECM components (fibronectin) and basement membrane (laminin, proteoglycans, collagen IV)
Composition of basal lamina
glycoprotein
adhesion molecule (laminin, fibronectin, entactin, thrombospondin)
proteoglycans (heparan sulfate chains)
microfibrils of collage IV and V (5 nm in diameter)
Sublayers of the tunica intima
Endothelium
Basal lamina
Reticular layer
Internal elastic lamina
Reticular layer of the tunica intima
Composition
Collagen types I and III
Proteoglycan: what it is, function in vascular wall, main types
macromolecules that influence viscoelasticity, permeability, lipid metabolism, homeostasis, thrombosis
Heparan sulfate
Dermatan sulfate
Chondroitin sulfate
Collagen: what it is, function in vascular wall, main types
Type IV collagen: made by EC and SMC; in the basement membrane
- high proline triple helix structure: affects flexibility and enhance cell adhesion and migration
Type V collagen: pericellular, made by EC and SMC
- bind interstitial collagen to cell/basal laminae
Type I collagen: major collagen; main type in human aorta intima and media
Type III collagen: major collagen; subendothelium of young adults
Describe: laminin
noncollagenous basement membrane
pivotal role in cell-basement membrane interactions
Describe: fibronectin
large glycoprotein with two disulfide-linked subunits
promote adhesion of molecules, spread of mesenchymal and epithelial cells and proliferation and migration of embryonic and tumor cells
Regulartes cell differentiation, shape, cytoskeletal organization
Thickness of internal elastic lamina
70-100 nm
Organization of the internal elastic lamina
Elastin organized into fenestrated cylindrical lamellae
Lamellae separated from neighbors by single layer SMC
Thickness and circumference can change with changes in media (in disease)
Tunica media: composition
Vascular SMC, elastin, collagen fibers arranged in organized fashion
SMC surrounded by basement membrane (laminin, collagen IV, heparans ulfate proteoglycan, entactin/nidogen, fibronectin)
- prevents migration of SMC
- maintains contractile state (not synthetic state SMC)
Synthetic state of SMC
Migrate to intima
proliferates
secrets ECM components
Strength layer collagen type of SMC
Type III
Average tangential tension per medial layer
2000 dynes/cm
Elastic arteries vs musclar arteries
Elastic arteries: well-defined elastic lamellae and collagen
- aorta, brachiocephalic trunk, iliac arteries
- lamellar units: elastin, collagen, SMCs
Muscular arteries: SMCs with fewer connective tissue fibres
- predominate in 2nd or 3rd order branches of elastic arteries
Average number of lamellar units in aorta
40-60 units
12-17 microm from arterial lumen
Number of lamellar units decrease from heart to peripheral arteries
Fascicles of the tunica media
Further organization of the SMC and branching elastic fibres
Each fascicle = sheath of basal lamina and collagen fibrils
Orientation of fascicle is in same direction of imposed tensile stress
- circumferentially in straight segments
- smaller and less uniform in size and orientation at bends and branching points
Tunica adventitia: composition
Vasa vasorum
Nerves: control SMC function
Fibrous connective tissue (elastic + collagen fibers)
Lymphatic network
Vaso vasorum: which vessels have them
Arteries > 200 microm
Arteries where medial layer > 29 lamellar units
Supply outer part of media while inner part is supplied by lumenal flow
Arise from parent artery at branch junctions
Pathophysiology of vasa vasorum in diseases
Flow affected by hypertension, mural stresses and deformations
Anatomy: track of the aorta
Left ventricle (3 cm)
arch back over root of left lung
descend within thorax on L of vertebral column
through aortic hiatus
ends opposite to lower L4 (1.75 cm)
Differences in small arteries vs larger arteries
Smaller arteries are musclar arteries
more innervated and principal regulators of peripheral resistance
thinner tunica intima
well defined internal elastic lamina
incomplete external elastic lamina
Unique anatomic features of coronary arteries
Thicker adventitia (collagen, elastic fibers, adipose tissue - predominate collagen \> elastic: greater tensile strength, low stretch
Richly innervated SMC in medial and adventitia
Branching sites of artery show normal periodic thickening of intima
Define: musculoelastic cushions
Thickening of intima at branching sites in coronary arteries
May contribute to atherosclerosis
May be a normal phenomenon
What vessel type is responsible as the chief source of vascular resistance
Arterioles
Composition of capillaries
Only tunica intima
Endothelium, basal lamina, pericytes (incomplete surrounding)
Function of pericytes
Contractile properties: regulate flow in capillaries
Differentiate into endothelial or SMC in remodeling and repair
Three types of capillaries
Continuous: selective filter by endothelium and lamina
Fenestrated: openings in endothelium; complete basal lamina
Discontinuous: incomplete endothelium, incomplete basal lamina
- sinusoid capillaries in liver, spleen, red bone marrow
Diameter of capillaries
4-15 microm
Size of fenestrations in fenestrated capillaries
50-60 nm
Size of Intercellular gaps in discontinuous capillaries
0.1 - 1 microm
Principle of vascular remodeling
Increase circumferential stress = increase SMC hypertrophy, collagen, elastin production
Decrease circumferential stress = vascular atrophy
Effect of chronic shear stress
Enhance L-arginine/NO pathway in endothelium –> mRNA cGMP –> matrix metalloproteinases (MMP-2, MMP-9)
- apoptosis, enlargement, vascular remodeling
Upregulation Type III NO synthase
Effect of age on arterial circumference
Medial thickness unchanged
Intimal thickness increased
Lumen diameter increased
Maintain consistent tensile strength
Principle of pressure-induced arterial wall crush
When there is limited vascular stretch, intraluminal pressure causes crush (same as in PTA treatment)
- DNA synthesis, cell proliferation (FGF2)
Endothelium response to shear stress
Align in direction of stress (elongation of cells)
Redistribution of intracellular stress fibers and quantity
Higher stress fibers (actin, myosin, contractile proteins)
*only occurs in arteries, not in veins
Activate stretch-induced ion channels, phospholipids and integrins
Upregulate PDGFs alpha and beta, TPA, TGF beta, endothelin-1, NO synthase III and ICAM-1
Different vessel wall layer response to cyclic/circumferential stretch
Endothelium: Cell proliferation (max in 1st day of exposure)
- Increase total protein content
SMC: change orientation (align perpendicularly to direction of strain vector; annular)
- increase type I and III collagen
- increase elastin
Fibroblast: increase type II:I collagen ratio
Venous endothelial cells produce these
Vasorelaxants: prostacyclin (PGI2) and NO
Venous media differes from arteries
Thinner layer, less well developed
Contribute to varicosity development
SMC held in quiescent state
TGF beta reduces mitogenesis and stabilize matrix
Heparin-like molecule neutralize FGF to downregulate proliferation
Venous adventitia differs from arteries
Thickest layer in large veins
can blend with the media
Vasa vasorum penetrate deeper
Vasa vasorum in veins differ from arteries
Much more extensive and penetrate deeper into adventitia
Likely due to lower oxygen tension in venous blood
Cellular signalling pathway for differentiation of artery and vein
Effect of Ephrin-B2 signalling
Regulates mural-cell migration, spreading and adhesion during wall assembly
Absence will limit mural cell recruitment
Effect of EphB4
limits cell proliferation, decreased intimal and medial thickening
Vein composition difference with artery
Vein more collagen, nearly no elastic fibers
Veins has diminished internal and external elastic laminae
Types of venules (3)
Characteristics and functions
Postcapillary venules: 10-50 microm in diameter
- endothelium and pericytes, no SMC
- loosely organized endothelium is leaky
- thin basal lamina
- main site for WBC diapedesis and tissue exudate
Collecting venules: similar with more pericytes
Muscular venules: clearly defined intimal layer, no elastic fibers, tunica media with 1-2 layers of SMC
Average size range of small-medium veins
1-9 mm diameter
Vessel wall anatomy of the venae cavae
Intima: fibroelastic tissue
Media: narrow with circumferentially oriented SMC
Adventitia: thick, longitudinally oriented collagen and SMC
Elastic fibers scattered throughout all layers; small amounts of cardiac tissue near connection to heart; extensive vasa vasorum in adventitia
Threshold of reverse velocity for venous valve closure
30 cm/s
Composition of venous valves
Collagen-elastic fiber core of connective tissue covered by thin endothelium
General location of venous valves
Distal to confluence of minor venous branches forming larger veins
Direction of intervenous flow in the lower extremity
Caudal to cephalad
Superficial to deep
Deep to superficial in dorsum of foot
Venous valve changes in venous insufficiency
Reduction in valves per unit length
Infiltration by monocytes and macrophages
Increased MMP-2 and MMP-9 favoring accumulation of ECM
Lymphatic drainage system names from extracellular back to vein
Extracellular matrix
Lymphatic capillaries (initial lymphatics; terminal lymphatics)
Precollecting lymphatics
Collecting lymphatics
Trunks
Ducts
Initial lymphatics: location
Blind-ended vessels
- connective tissue of skin and liver
- mucous membrane of resp, GI, GU
Diameter of initial lymphatics
10-60 microm
Thickness of initial lymphatics and wall composition
50-100 nm
monolayer nonfenestrated endothelial cells
Discontinuous or absent basal lamina
What is the endothelial microvalve
Gaps between endothelial cells are 10 microm
When vessels collapsed, gaps open allowing for lymphatic entry
When vessels filled, cells expand and close gaps
- therefore unidirectional flow
Precollecting lymphatics propulsion system
Secondary valves: bicuspid, irregularly spaced, sometimes single leaflet
SMC contractions
Primary valves as in initial lymphatics
Collecting lymphatics: wall anatomy
No more primary valve mechanism
3 typical vessel layers
- intimal monolayer
- SMC, collagen, elastic fiber 1-3 layers (helicoidal manner)
- adventitia: fibroblast, connective tissue, nerve terminals
More regularly spaced secondary valves
Lymphangions
definition
diameter and length
Space between two secondary valves
In head and neck: 0.2 mm diameter, 2 mm length
Lower extremity: 1-2 mm diameter, 2 mm length
Innervated by SNS and PNS
Lymph node anatomy
Secondary valves
anatomy
Lymphatic vessel wall bulges at secondary valves
- causes string of pearls because of diameter changes
Monolayer of endothelial cells on a collagen matrix
Cisterna chyli
Define
Confluence of lymphatic vessels from lower extremity by way of inguinal lymph nodes
Factors involved in lymphatic propulsion
Primary valves
Secondary valves
Rhythmic contractions of SMC (pacemaker cells)
